Many different materials have been investigated to resist non-specific protein adsorption. Chemistries utilized for this purpose include, but are not limited to: polyethers (e.g., polyethylene glycol), polysaccharides such as dextran, hydrophilic polymers such as polyvinylpyrrolidone or hydroxyethyl-methacrylate, heparin, intramolecular zwitterions or mixed charge materials, and hydrogen bond accepting groups such as those described in U.S. Pat. No. 7,276,286. The ability of these materials in preventing protein adsorption varies greatly between the chemistries. Of these materials, only a few resist fouling to the degree required for short-term in vivo application. However, the few materials appropriate for short-term application, when used for longer periods of time in complex media or in vivo, exhibit significant fouling or other degradation, making them unsuitable for long-term applications. Furthermore, surfaces coated with materials that resist in vivo degradation are often susceptible to a noticeable decrease in fouling resistance over time.
Biocompatible coatings, especially those applied to medical device substrates, have been applied by dip coating the substrate in a single polymer solution. For hydrophilic polymers applied to hydrophobic substrates, this approach presents many challenges as it can be difficult to form stable coatings. In an attempt to improve stability, hydrophilic materials have been cross-linked or copolymerized with hydrophobic groups. However, such approaches can have significant negative effects on the overall coating performance, especially when resistance to protein adsorption is desired.
Conventional fouling resistant or non-fouling materials and surface coatings are susceptible to fouling over prolonged exposure to complex media or in vivo environments. The materials used for many non-fouling and fouling resistant coatings, or the tethers used to immobilize the coatings on a substrate, have not, to date, possessed the stability required to coat the substrate for extended periods of time, for example, at least 7, 14, 30, 60, 90, 120, 365, or 1000 days.